3D ultrasound will be combined with a full-field digital mammography (DX) system via an automatic scanning mechanism on the DX gantry. It is proposed to take full advantage of the many synergisms among an innovative combination of modes of these two modalities for breast cancer diagnosis, and, eventually, detection. The basic and advanced modes implemented and tested in the system are those which should provide relatively independent information about the breast tissues and with which we have extensive, related research experience in the numerous breast imaging groups at the University of Michigan and/or General Electric. Advanced modes include tomosynthesis which, unlike projection imaging, gives x-ray interaction properties of the specific tissues evaluated by the ultrasound methods. Nonlinear elasticity and 3D color flow imaging by ultrasound (UL) provide mechanical and physiological information unavailable from conventional, noncontrast x-ray and ultrasound imaging. Compound and single-view US imaging are complimentary, with the former providing better distal tumor borders and other features helpful to visual and computer-aided diagnosis. In a single positioning, with possible variation in compression, the breast will be imaged by: 1) the basic modes -- projection digital x-ray and full field 3D gray scale ultrasound: 2) the advanced modes -- 3D x-ray tomosynthesis and advanced ultrasound of the mass region (nonlinear elasticity, 3D color flow, and compound imaging). In the main clinical evaluations on 160 women with masses going to biopsy and 40 with simple cysts, the basic and advanced imaging modes will be compared on the same patients and good combinations of modes revealed. The first hypothesis is that the basic combined technique is diagnostically equivalent to the current best practice of high quality mammography plus hand-held ultrasound performed by MQSA-certified radiologists. Linear combinations of the basic and advanced modes will be evaluated for relative diagnostic accuracy. Clinical evaluation of the potential of the combined system for screening of selected populations must follow demonstration of diagnostic equivalence. Developments will be done to objectively illustrate some of the approaches and potential of visual and computer aided diagnosis (CAD) and detection with these multiple modes. In addition to the coregistration inherent in the combined system, image based registration will be applied to correct for modestly differing views, compressions and tissue motions between modalities, modes, UL transducer sweeps, and studies at different times.